Regulatory mechanism of osteoclasts by hormones produced in osteoblasts: analysis using fish scales as a bone model

• Project/Area Number: 20K06718
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44040:Morphology and anatomical structure-related
• Research Institution: Kanazawa University
• Principal Investigator: Suzuki Nobuo 金沢大学, 環日本海域環境研究センター, 教授 (60242476)
• Co-Investigator(Kenkyū-buntansha): 小林 功 金沢大学, 生命理工学系, 准教授 (30774757) ; 関口 俊男 金沢大学, 環日本海域環境研究センター, 准教授 (40378568) ; 服部 淳彦 東京医科歯科大学, 教養部, 教授 (70183910) ; 平山 順 公立小松大学, 保健医療学部, 教授 (90510363)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 魚類のウロコ / ラットの頭蓋骨 / 骨芽細胞 / 破骨細胞 / メラトニン / カルシトニン / ウロコ / カルシトニンの機能阻害 / カルシトニン遺伝子の機能阻害

Outline of Research at the Start

本研究では、①ウロコの再生過程におけるメラトニン合成及びカルシトニンの発現を調べて、ウロコの再生過程におけるホルモンの発現及び骨芽細胞と破骨細胞の相互作用を解析する。②カルシトニンを機能阻害をして、ウロコの再生に及ぼす影響を解析する。機能阻害の影響が、カルシトニン添加によりレスキューされるかについても調べる。③哺乳類の細胞を用いて、メラトニンによるカルシトニンの発現調節を調べる。ラットの骨芽細胞でカルシトニンの発現を免疫染色により確認しており、哺乳類で検証して、メラトニンの骨代謝制御の確証を目指す。

Outline of Final Research Achievements

Fish scales are bone-like tissues in which bone-formative cells (osteoblasts) and bone-resorptive cells (osteoclasts) coexist. The presence of these cells on the body surface facilitates whole-mount morphological analysis. Noting these characteristics, we have developed an assay system using scales as a bone model to investigate the effects of various hormones. In the present study, we focused on hormones expressed in scales and examined the expression of hormones (melatonin and calcitonin) produced by osteoblasts during scale regeneration. Next, hormonal treatments were applied to scales, and their effects on osteoblasts were analyzed. Mammalian bone cells were then subjected to the same hormone treatments as fish scales to examine the reproducibility of the results obtained in fish.

Academic Significance and Societal Importance of the Research Achievements

これまで、メラトニン及びカルシトニンは特定の内分泌腺から分泌され、分泌されたホルモンが骨に作用していると考えられていた。本研究により、魚類のウロコのみならず哺乳類の細胞（ラットの頭蓋骨及びヒトの骨芽細胞）においても、骨芽細胞で作られて、局所的に作用していることを見出すことができた。魚類のウロコを骨モデルとして用いて、哺乳類の骨芽細胞においても同様な作用を見出すことができたので、その意義は大きい。

Research Products

• [Int'l Joint Research] D.D.U. Gorakhpur University(インド)
• [Int'l Joint Research] D.D.U. Gorakhpur University(インド)
• [Journal Article] Possible involvement of Calcitonin I and II in calcium metabolism of the female reproductive physiology of goldfish (Carassius auratus). (2023)
  • Author(s): Kuroda, K., Hatano, K., Kawamura, R., Fukushima, A., Sasayama, Y., Tabuchi, Y., Furusawa, Y., Ikegame, M., Hattori, A., Hirayama, J., Fukuda, T., Uekura, S., Matsubara, H., Kawago, U., Sekiguchi, T., Srivastav, A.K. and Suzuki, N.
  • Journal Title: Int. Aquat. Res., 15: 15-26 (2023) Volume: 15 Pages: 15-26
• [Journal Article] Activation of RANKL-producing cells under simulated microgravity with a three-dimensional clinostat in regenerating goldfish scales (2022)
  • Author(s): Yamamoto, T., Ikegame, M., Kuroda, K., Kobayashi-Sun, J., Hirayama, J., Kobayashi, I., Kawamura, R., Endo, M., Tabuchi, Y., Furusawa, Y., Yachiguchi, K., Sekiguchi, T., Matsubara, H., Yano, S., Hattori, A. and Suzuki, N.
  • Journal Title: Biological Sciences in Space Volume: 36 Issue: 0 Pages: 9-14
  • DOI: 10.2187/bss.36.9
  • ISSN: 0914-9201, 1349-967X
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Osteoclastic and Osteoblastic Responses to Hypergravity and Microgravity: Analysis Using Goldfish Scales as a Bone Model (2022)
  • Author(s): Yamamoto Tatsuki、Ikegame Mika、Furusawa Yukihiro、Tabuchi Yoshiaki、Hatano Kaito、Watanabe Kazuki、Kawago Umi、Hirayama Jun、Yano Sachiko、Sekiguchi Toshio、Kitamura Kei-ichiro、Endo Masato、Nagami Arata、Matsubara Hajime、Maruyama Yusuke、Hattori Atsuhiko、Suzuki Nobuo
  • Journal Title: Zoological Science Volume: 39 Issue: 4 Pages: 388-396
  • DOI: 10.2108/zs210107
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Oral administration of melatonin increases plasma calcium and magnesium and improves bone metabolism in aged male mice (2021)
  • Author(s): Igarashi-Migitaka Junko、Maruyama Yusuke、Seki Azusa、Hirayama Jun、Kamijo-Ikemori Atsuko、Hirata Kazuaki、Kawamura Ryoya、Matsubara Hajime、Srivastav Ajai K、Tabuchi Yoshiaki、Mishima Hiroyuki、Hattori Atsuhiko、Suzuki Nobuo
  • Journal Title: Melatonin Research Volume: 4 Issue: 4 Pages: 581-591
  • DOI: 10.32794/mr112500113
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Influence of estrogen and the endocrine disruptor on the calcitonin functions in teleosts. (2021)
  • Author(s): Sekiguchi, T., Srivastav, A.K. and Suzuki, N.
  • Journal Title: International Journal of Biological and Environmental Investigations Volume: 1 Issue: 2 Pages: 134-140
  • DOI: 10.33745/ijbei.2021.v01i02.002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression of sclerostin in the regenerating scales of goldfish and its increase under microgravity during space flight (2020)
  • Author(s): Yamamoto, T., Ikegame, M., Hirayama, J., Kitamura, K., Tabuchi, Y., Furusawa, Y., Sekiguchi, T., Endo, M., Mishima, H., Seki, A., Yano, S., Matsubara H., Hattori, A. and Suzuki, N.
  • Journal Title: Biomedical Research Volume: 41 Issue: 6 Pages: 279-288
  • DOI: 10.2220/biomedres.41.279
  • NAID: 130007948844
  • ISSN: 0388-6107, 1880-313X
  • Year and Date: 2020-12-01
  • Peer Reviewed / Open Access
• [Journal Article] Detection of RANKL-producing cells and osteoclastic activation by the addition of exogenous RANKL in the regenerating scales of goldfish. (2020)
  • Author(s): Yamamoto, T., Ikegame, M., Kawago, U., Tabuchi, Y., Hirayama, J., Sekiguchi, T., Furusawa, Y., Yachiguchi, K., Matsubara, H., Urata, M., Hattori, A. and Suzuki, N.
  • Journal Title: Biological Science in Space Volume: 34 Issue: 0 Pages: 34-40
  • DOI: 10.2187/bss.34.34
  • NAID: 130007884615
  • Peer Reviewed / Open Access
• [Journal Article] Oral administration of melatonin contained in drinking water increased bone strength in naturally aged mice (2020)
  • Author(s): Igarashi-Migitaka Junko、Seki Azusa、Ikegame Mika、Honda Masato、Sekiguchi Toshio、Mishima Hiroyuki、Shimizu Nobuaki、Matsubara Hajime、Srivastav Ajai K.、Hirayama Jun、Maruyama Yusuke、Kamijo-Ikemori Atsuko、Hirata Kazuaki、Hattori Atsuhiko、Suzuki Nobuo
  • Journal Title: Acta Histochemica Volume: 122 Issue: 6 Pages: 151596-151596
  • DOI: 10.1016/j.acthis.2020.151596
  • Peer Reviewed / Int'l Joint Research
• [Presentation] キンギョのメスの生殖生理におけるカルシトニンI 及びIIの役割 (2023)
  • Author(s): 黒田康平、端野開都、川村龍矢、笹山雄一、福島綾香、田渕圭章、古澤之裕、池亀美華、服部淳彦、平山 順、松原 創、河合 海、関口俊男、Srivastav AK、鈴木信雄
  • Organizer: 5年度日本水産学会春季大会
• [Presentation] Calcitonin I and II possible involvement of calcium metabolism in the female reproductive physiology of goldfish (Carassius auratus). (2022)
  • Author(s): Kuroda, K., Hatano, K., Kawamura, R., Fukushima, A., Sasayama, Y., Tabuchi, Y., Furusawa, Y., Ikegame, M., Hattori, A., Hirayama, J., Matsubara, H., Kawago, U., Sekiguchi, T., Srivastav, A.K. and Suzuki, N.
  • Organizer: oint Usage/Joint Research on Transboundary Pollution and its Impact on Social Environment, Kanazawa University, Ishikawa, Japan
  • Int'l Joint Research
• [Presentation] カルシトニンIに加えてカルシトニンIIもキンギョの雌の生殖生理に関与する (2022)
  • Author(s): 黒田康平，端野開都，川村龍矢，笹山雄一，福島綾香，田渕圭章，古澤之裕，池亀美華，服部淳彦，平山 順，松原 創，河合 海，関口俊男，Srivastav AK，鈴木信雄
  • Organizer: 第46回日本比較内分泌学会大会東京大会
• [Presentation] 宇宙空間で引き起こされる骨吸収を抑制する新規治療薬の作用 (2021)
  • Author(s): 関あずさ，山本 樹，田渕圭章，古澤之裕，関口俊男，矢野幸子，北村敬一郎，高垣裕子，池亀美華，染井正徳，松原 創，平山 順，服部淳彦，鈴木信雄
  • Organizer: 日本宇宙生物科学会第35回大会
• [Presentation] メラトニンとその合成分子の発現へ重力変化の影響 (2021)
  • Author(s): 平山 順, 鈴木 信雄 , 柴田 眞寛, 服部 淳彦
  • Organizer: 日本宇宙生物科学会第35回大会
• [Presentation] メイラード反応と糖尿病合併症の関係 (2021)
  • Author(s): 平山 順，北村敬一郎，鈴木信雄
  • Organizer: 第31回日本メイラード学会年会
• [Presentation] Toxic effect of the polycyclic aromatic hydrocarbons (PAHs) in aquatic animals with special references to calcium metabolism. (2021)
  • Author(s): Suzuki N
  • Organizer: Chozen International Symposium on Understanding the Transboundary Pollution along North-South Transect in western Pacific region
  • Int'l Joint Research / Invited
• [Presentation] Glyoxal-induced formation of carboxymethyl arginine in type 1 collagen decreases both its strength and flexibility in vitro. (2021)
  • Author(s): Hirayama, J., Kitamura, K., Tabuchi, Y., Minami, T., Matsubara, H., Hattori, A. and Suzuki, N.
  • Organizer: International Maillard Reaction Society-14
  • Int'l Joint Research
• [Presentation] Detection of RANKL-producing cells and osteoclastic activation by the addition of RANKL in the regenerating scales of goldfish. (2020)
  • Author(s): Yamamoto, T., Ikegame, M., Kawago, U., Tabuchi, Y., Hirayama, J., Sekiguchi, T., Furusawa, Y., Yachiguchi, K., Matsubara, H., Urata, M., Hattori, A. and Suzuki, N.
  • Organizer: Joint International Symposium: Challenging the Research Development and Collaboration Through Online Discussions
  • Int'l Joint Research
• [Presentation] Effect of melatonin on bone metabolism in naturally aged mice. (2020)
  • Author(s): Migitaka, J., Seki, A., Hattori, A. and Suzuki, N.
  • Organizer: Joint International Symposium: Challenging the Research Development and Collaboration Through Online Discussions
  • Int'l Joint Research
• [Presentation] メラトニンは骨芽細胞で産生されるカルシトニンの分泌を促進する (2020)
  • Author(s): 鈴木信雄，池亀美華，田渕圭章，古澤之裕，北村敬一郎，関口俊男，山本 樹，矢野幸子，平山 順，服部淳彦
  • Organizer: 日本動物学会
• [Presentation] 宇宙空間における骨代謝制御：キンギョの培養ウロコを骨のモデルとした解析 (2020)
  • Author(s): 鈴木信雄
  • Organizer: 日本宇宙生物科学会
  • Invited
• [Book] Calcitonin In "Handbook of Hormones: Comparative Endocrinology for Basic and Clinical Research" (2021)
  • Author(s): N. Suzuki
  • Total Pages: 4
  • Publisher: ELSEVIER
  • ISBN: 9780128206492